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Study of ProMetic BioTherapeutics Immune Globulin Intravenous (Human) 10%

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02269163
Recruitment Status : Completed
First Posted : October 20, 2014
Last Update Posted : March 5, 2020
Sponsor:
Collaborator:
Atlantic Research Group
Information provided by (Responsible Party):
Prometic Biotherapeutics, Inc.

Brief Summary:
Phase 3 multicenter, open-label study of safety, tolerability, efficacy, and pharmacokinetics (PK) of ProMetic's Immune Globulin Intravenous (Human) 10%, the investigational medicinal product [IMP]), in Adults and Children with Primary Immunodeficiency Diseases (PIDD).

Condition or disease Intervention/treatment Phase
Primary Immunodeficiency Biological: Immune Globulin Intravenous Biological: Prometic's Immune Globulin Intravenous 10% Phase 3

Detailed Description:

This is a pivotal Phase 3, open-label, single-arm, multicenter study to assess the tolerability, safety, efficacy, and Pharmacokinetics of the Investigational Medicinal Product in adults and children with Primary Immunodeficiency Diseases (PIDD). A total of approximately 75 subjects aged 2-80 years will be enrolled in the study. Subjects who switch from an investigational immune globulin or subcutaneous immune globulin (IGSC) are required to receive a stable dose of commercial product (CP), which is a licensed commercially available immune globulin intravenous (IGIV) product for at least 3 cycles before they can be given the Investigational Medicinal Product . This study schema will result in the Commercial Product Treatment Period and Investigational Medicinal Product Treatment Period. All subjects will be treated on an outpatient basis with the Investigational Medicinal Product for approximately 1 year, with the dose and schedule based on their previous IGIV treatment regimen (21-day or 28-day dosing interval). A subset of subjects will participate in a Pharmacokinetics sub-study.

The primary objective of the study is to examine the rate of clinically documented serious bacterial infections (SBIs) in subjects treated with the Investigational Medicinal Product to achieve a rate of less than one SBI per year.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 82 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 3, Multicenter, Open-Label Study of the Safety, Tolerability, Efficacy, and PK of ProMetic BioTherapeutics IGIV (Human) 10% in Adults and Children With Primary Immunodeficiency Diseases
Actual Study Start Date : January 26, 2016
Actual Primary Completion Date : January 11, 2019
Actual Study Completion Date : January 11, 2019


Arm Intervention/treatment
Active Comparator: Gammargard, Gammaplex, Gamunex, or Octogam Treatment Period
Subjects who enroll in the study while on Gammargard, Gammaplex, Gamunex, or Octogam IGIV Product and need to wait for the scheduled start of Prometic IGIV (10%) treatment will continue on their usual dose and treatment cycle with Gammargard, Gammaplex, Gamunex, or Octogam IVIG Product during this period.
Biological: Immune Globulin Intravenous
Gammargard, Gammaplex,Gamunex, or Octogam IGIV Product

Experimental: Prometic IGIV 10% Treatment Period
Subjects will receive Prometic Immune Globulin Intravenous 10%
Biological: Prometic's Immune Globulin Intravenous 10%
Liquid formulation of Prometic Immune Globulin Intravenous 10% (human) in 50 mL vials containing 100 mg/mL of immunoglobulin G (IgG)




Primary Outcome Measures :
  1. Annual rate of occurrence of SBI [ Time Frame: One year ]
    SBIs will be calculated for each subject as 52n/w, where n is the number of reported SBIs and w is the number of weeks on study


Secondary Outcome Measures :
  1. Trough levels of IgG (Total) prior to each Prometic IGIV 10% infusion [ Time Frame: One year ]
    Subject's total IgG levels will be assessed prior to each Prometic IGIV 10% infusion

  2. Number of days out of work/school/kindergarten/day care or inability to perform normal daily activities due to infections [ Time Frame: One year ]
    Annualized rate for this outcome measure will be determined

  3. Number of days of hospitalizations due to infections [ Time Frame: One year ]
    Annualized rate for this outcome measure will be determined

  4. Number of episodes of fever (≥100.4°F) [ Time Frame: One year ]
    Annualized rate will for this outcome measure will be determined

  5. Number of days of antibiotics used for infection prophylaxis or treatment [ Time Frame: One year ]
    Annualized rate for this outcome measure will be determined

  6. Number of infections other than serious bacterial infections [ Time Frame: One year ]
    Annualized rate for this outcome measure will be determined

  7. Determine steady state serum concentrations of total IgG [ Time Frame: Subjects will have blood samples drawn for PK analysis before and after Infusion 6 for 21-day cycle subjects or Infusion 5 for 28-day cycle subjects at specified time points ]
    IgG concentration will be baseline-corrected using the trough level obtained immediately prior to infusion as baseline.


Other Outcome Measures:
  1. Incidence of treatment-emergent adverse events (TEAEs) [ Time Frame: One year ]
    • The relatedness and severity of all TEAEs will be summarized
    • Immunogenic reaction will be monitored by testing for antibodies against ß2 glycoprotein I (ß2GPI) and to ß2GPI domain I (ß2GPI DI)
    • Thrombogenicity and hemolysis will be monitored

  2. Incidence of temporally associated adverse events (TAAEs) defined as TEAEs that occur within 72 hours following infusion [ Time Frame: One year ]
    Subjects will be monitored for infusional TEAEs during the infusions, for 3-4 hours after the first infusion, and for 1 hour after further infusions. All subjects will be monitored for temporally associated TEAEs in the 24-hour and 72-hour phone calls from staff.

  3. The number and proportion of infusions with which one or more TAAEs and infusional TEAEs are associated [ Time Frame: One year ]
    Subjects are monitored for infusional TEAEs during the infusions, for 3-4 hours after the first infusion, and for 1 hour after further infusions.

  4. The number of TAAEs and infusional TEAEs per infusion [ Time Frame: One year ]
  5. Number of infusions/subject where infusion rate was decreased due to an TEAE [ Time Frame: One year ]
    Infusional and temporally associated TEAEs will be closely monitored. If an infusional TEAE occurs during the first treatment course, the study staff will initiate measures to decrease the rate of infusion as specified in the protocol

  6. Number of subjects with at least one infusion where rate was decreased due to an TEAE [ Time Frame: One year ]
    Infusional and temporally associated TEAEs will be closely monitored. If an infusional TEAE occurs during the first treatment course, the study staff will initiate measures to decrease the rate of infusion as specified in the protocol



Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years to 80 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subject is male or female between the ages of 2 and 80 years at Screening.
  2. Female subjects of childbearing potential must agree to employ adequate birth control measures, as determined by their IRB/IEC, for the duration of the study.
  3. The subject must have one of the following three diagnoses (isolated PIDD of other types will be excluded):

    • Common variable immunodeficiency
    • X-linked agammaglobulinemia
    • Hyper-IgM syndrome and documented low IgG levels (<4.5 mg/mL [450 mg/dL]).
  4. Subjects must have been treated with a stable dose of immune globulin administered intravenously (IGIV) or subcutaneously (IGSC) and has documented trough or steady state IgG levels of ≥ 5 mg/mL.

Exclusion Criteria:

  1. Subject has secondary immunodeficiency or has been diagnosed with dysgammaglobulinemia or isolated IgG subclass deficiency; has known hypoalbuminemia (<3 gm/dL), protein-losing enteropathy, or nephrotic syndrome.
  2. Subject has ever had a history of severe anaphylactic or anaphylactoid reaction to immunoglobulins or other blood products.
  3. Subject has a known history of immunoglobulin A (IgA) deficiency and known anti-IgA antibodies, thrombotic event, such as deep vein thrombosis, myocardial infarction, cerebrovascular accident, pulmonary embolism, at any time.
  4. Subject has received blood products except IGIV, IGSC, or albumin within the previous 12 months or has participated in another study (except for IGIV, IGSC studies) within the previous 4 weeks.
  5. Subject has had cancer in the past 5 years, except for basal cell or squamous cell cancers of the skin.
  6. Subject has had a documented active infection within 7 days prior to Screening, or subject is on continuous prophylactic antibiotics.
  7. Subject is positive for human immunodeficiency virus (HIV)-1 or HIV-2, a positive hepatitis C virus (HCV) or hepatitis B virus (HBV).
  8. Subject has levels of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5 times the upper limit of normal (ULN).
  9. Subject has serum creatinine >1.5 times the ULN or a severe chronic condition such as renal failure with proteinuria.
  10. Subject has anemia with a hemoglobin level ≤8 g/dL.
  11. Subject has severe neutropenia with neutrophil count ≤1000 per mmᴧ3 or has lymphopenia with <500 per/ mmᴧ3.
  12. Subject is taking prednisone at a dose ≥0.15 mg/kg/day and receiving other immunosuppressive drugs or chemotherapy.
  13. Subject has known atrial fibrillation requiring anticoagulant therapy; congestive heart failure (New York Heart Association Class III/IV); cardiomyopathy; or cardiac arrhythmia associated with thromboembolic events, unstable or advanced ischemic heart disease, or hyperviscosity.
  14. Subject has known decreased Protein C and/or Protein S levels.
  15. Subject is positive for antibodies to β2GPI and/or β2GPI DI at Screening.
  16. Female subject who is pregnant, breast-feeding, or planning a pregnancy during the course of the study.
  17. A history of epilepsy or multiple episodes of migraine (defined as at least one episode within 6 months of enrolment) not completely controlled by medication, or any condition that is likely to interfere with evaluation of the IMP or satisfactory conduct of the study in the Investigator's opinion.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02269163


Locations
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United States, California
University of California, Irvine
Irvine, California, United States, 92697
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
United States, Colorado
Immunoe International Research
Centennial, Colorado, United States, 80112
National Jewish Hospital
Denver, Colorado, United States, 80206
United States, Florida
Allergy Associates of the Palm Beaches
North Palm Beach, Florida, United States, 33408
Johns Hopkins All Children's Hospital
Saint Petersburg, Florida, United States, 33701
United States, Illinois
Rush University Medical Center
Chicago, Illinois, United States, 60612
United States, Indiana
Fort Wayne Medical Institute
Fort Wayne, Indiana, United States, 46815
United States, Missouri
St. Louis University
Saint Louis, Missouri, United States, 63104
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
Optimed Research
Columbus, Ohio, United States, 43236
United States, Texas
Dallas Allergy Immunology
Dallas, Texas, United States, 75230
United States, Washington
Bellingham Asthma, Allergy and Immunology Clinic
Bellingham, Washington, United States, 98225
Sponsors and Collaborators
Prometic Biotherapeutics, Inc.
Atlantic Research Group
Investigators
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Study Chair: James Moy, MD Rush University Medical Center
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Responsible Party: Prometic Biotherapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02269163    
Other Study ID Numbers: 2004C009G
First Posted: October 20, 2014    Key Record Dates
Last Update Posted: March 5, 2020
Last Verified: February 2020
Additional relevant MeSH terms:
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Immunologic Deficiency Syndromes
Immune System Diseases
Immunoglobulins
Antibodies
gamma-Globulins
Immunoglobulins, Intravenous
Rho(D) Immune Globulin
Immunoglobulin G
Immunologic Factors
Physiological Effects of Drugs